SARS-CoV-2 infection protects against rechallenge in rhesus macaques

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Abstract

An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log ₁₀ reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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Author and article information

Journal

Journal ID (nlm-ta): Science

Journal ID (iso-abbrev): Science

Journal ID (publisher-id): SCIENCE

Title: Science (New York, N.y.)

Publisher: American Association for the Advancement of Science

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date (Electronic): 20 May 2020

Electronic Location Identifier: eabc4776

Affiliations

[1 ]Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

[2 ]Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.

[3 ]Harvard Medical School, Boston, MA 02115, USA.

[4 ]Oregon Health & Sciences University, Beaverton, OR 97006, USA.

[5 ]University of North Carolina, Chapel Hill, NC 27599, USA.

[6 ]Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

[7 ]Bioqual, Rockville, MD 20852, USA.

[8 ]Janssen Vaccines & Prevention BV, Leiden, Netherlands.

[9 ]Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.

[10 ]Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: dbarouch@ 123456bidmc.harvard.edu

Author information

Abishek Chandrashekar https://orcid.org/0000-0001-7821-5552

Jinyan Liu https://orcid.org/0000-0003-0504-2181

Amanda J. Martinot https://orcid.org/0000-0001-6237-6191

Katherine McMahan https://orcid.org/0000-0002-3933-0539

Noe B. Mercado https://orcid.org/0000-0001-7769-7326

Lauren Peter https://orcid.org/0000-0002-2105-7503

Lisa H. Tostanoski https://orcid.org/0000-0001-9255-5684

Jingyou Yu https://orcid.org/0000-0002-0775-6623

Zoltan Maliga https://orcid.org/0000-0003-4209-7253

Kathleen Busman-Sahay https://orcid.org/0000-0002-8549-0023

Margaret Terry https://orcid.org/0000-0002-7260-9005

Linda M. Wrijil https://orcid.org/0000-0003-0786-8390

Sarah Ducat https://orcid.org/0000-0002-5285-7642

Caroline Atyeo https://orcid.org/0000-0002-7489-0232

Stephanie Fischinger https://orcid.org/0000-0003-2307-3379

John S. Burke https://orcid.org/0000-0003-1282-8211

Matthew D. Slein https://orcid.org/0000-0001-8288-787X

Laurent Pessaint https://orcid.org/0000-0002-2126-3008

Alex Van Ry https://orcid.org/0000-0002-1240-9044

Jack Greenhouse https://orcid.org/0000-0003-2325-8162

Tammy Taylor https://orcid.org/0000-0001-7367-3271

Kelvin Blade https://orcid.org/0000-0003-3387-6693

Brad Finneyfrock https://orcid.org/0000-0002-1564-5798

Roland Zahn https://orcid.org/0000-0003-2822-6231

Frank Wegmann https://orcid.org/0000-0002-9821-1492

Peter Abbink https://orcid.org/0000-0003-1978-088X

Esther A. Bondzie https://orcid.org/0000-0001-9409-5052

Gabriel Dagotto https://orcid.org/0000-0002-9872-6074

Makda S. Gebre https://orcid.org/0000-0001-8520-2178

Catherine Jacob-Dolan https://orcid.org/0000-0001-6641-0342

Nicole Kordana https://orcid.org/0000-0003-4082-6029

Michelle A. Lifton https://orcid.org/0000-0003-0279-2198

Shant H. Mahrokhian https://orcid.org/0000-0003-4094-8739

Lori F. Maxfield https://orcid.org/0000-0002-7595-6205

Ramya Nityanandam https://orcid.org/0000-0002-3288-8505

Joseph P. Nkolola https://orcid.org/0000-0002-0678-9765

Aaron G. Schmidt https://orcid.org/0000-0003-3627-2553

Andrew D. Miller https://orcid.org/0000-0001-6350-5581

Ralph S. Baric https://orcid.org/0000-0001-6827-8701

Galit Alter https://orcid.org/0000-0002-7680-9215

Peter K. Sorger https://orcid.org/0000-0002-3364-1838

Jacob D. Estes https://orcid.org/0000-0002-9652-6394

Hanne Andersen https://orcid.org/0000-0003-1103-9608

Mark G. Lewis https://orcid.org/0000-0001-7852-0135

Dan H. Barouch https://orcid.org/0000-0001-5127-4659

Article

Publisher ID: abc4776

DOI: 10.1126/science.abc4776

PMC ID: 7243369

PubMed ID: 32434946

SO-VID: a21740d3-3906-4987-947b-042a63c6453e

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 26 April 2020

Date accepted : 16 May 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: OD024917, AI129797, AI124377, AI128751, AI126603

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: AI135098

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: AI007151

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: AI146779

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: CA225088

Funded by: doi http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;

Award ID: INV-006131

Funded by: doi http://dx.doi.org/10.13039/100005205, Janssen Research and Development;

Award ID: N/A

Funded by: doi http://dx.doi.org/10.13039/100005615, Beth Israel Deaconess Medical Center;

Award ID: N/A

Funded by: doi http://dx.doi.org/10.13039/100012802, Ragon Institute of MGH, MIT and Harvard;

Award ID: N/A

Funded by: Mark and Lisa Schwartz Foundation;

Award ID: N/A

Funded by: Massachusetts Consortium on Pathogen Readiness;

Award ID: N/A

Funded by: doi http://dx.doi.org/10.13039/100000861, Burroughs Wellcome Fund;

Award ID: N/A

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: OD011092, OD025002

Funded by: Emergent Ventures, Mercatus Center;

Award ID: N/A

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

SARS-CoV-2 infection protects against rechallenge in rhesus macaques

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Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 13

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

A Novel Coronavirus from Patients with Pneumonia in China, 2019

A pneumonia outbreak associated with a new coronavirus of probable bat origin

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